Combination products with tyrosine kinase inhibitors and their use

Abstract

The present invention relates to pharmaceutical products comprising a combination of (i) a MET inhibitor and (ii) an EGFR inhibitor, or a pharmaceutically acceptable salt thereof, respectively, or a prodrug thereof, which are jointly active in the treatment of proliferative diseases, corresponding pharmaceutical formulations, uses, methods, processes, commercial packages and related invention embodiments.

1 - 13 . (canceled) 
     
     
         14 . A method of treating cancer, which comprises simultaneous, separate or sequential administration to a subject in need of such treatment,
 (i) a MET tyrosine kinase inhibitor which is 2-fluoro-N-methyl-4-[(7-quinolin-6-yl-methyl)-imidazo[1,2-b]triazin-2-yl]benzamide, or a pharmaceutically acceptable salt thereof, and   (ii) an EGFR tyrosine kinase inhibitor, or a pharmaceutically acceptable salt thereof.   
     
     
         15 . The method of  claim 14 , wherein the EGFR tyrosine kinase inhibitor is erlotinib, lapatinib, canertinib, pelitinib, neratinib, or cetuximab, or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 14 , wherein the cancer is breast cancer, gastric cancer, lung cancer, cancer of the prostate, bladder cancer or endometrial cancer. 
     
     
         17 . The method of  claim 14 , wherein the cancer is adenocarcinoma, rhabdomyosarcoma, osteosarcoma, urinary bladder carcinoma, colorectal cancer or glioma. 
     
     
         18 . The method of  claim 14 , wherein the cancer is lung cancer. 
     
     
         19 . The method of  claim 14 , wherein the cancer is non-small cell lung cancer. 
     
     
         20 . A method of treating cancer, which comprises simultaneous, separate or sequential administration to a subject in need of such treatment,
 (i) a MET tyrosine kinase inhibitor which is 2-fluoro-N-methyl-4-[(7-quinolin-6-yl-methyl)-imidazo[1,2-b]triazin-2-yl]benzamide, or a pharmaceutically acceptable salt thereof, and   (ii) an EGFR tyrosine kinase inhibitor, or a pharmaceutically acceptable salt thereof, wherein the subject has developed resistance to EGFR inhibitor treatment.   
     
     
         21 . The method of  claim 20 , wherein the EGFR tyrosine kinase inhibitor is erlotinib, lapatinib, canertinib, pelitinib, neratinib, or cetuximab, or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 20 , wherein the cancer is breast cancer, gastric cancer, lung cancer, cancer of the prostate, bladder cancer or endometrial cancer. 
     
     
         23 . The method of  claim 20 , wherein the cancer is adenocarcinoma, rhabdomyosarcoma, osteosarcoma, urinary bladder carcinoma, colorectal cancer or glioma. 
     
     
         24 . The method of  claim 20 , wherein the cancer is lung cancer. 
     
     
         25 . The method of  claim 20 , wherein the cancer is non-small cell lung cancer. 
     
     
         26 . A method of treating cancer, which comprises simultaneous, separate or sequential administration to a subject in need of such treatment, (i) a MET tyrosine kinase inhibitor which is 2-fluoro-N-methyl-4-[(7-quinolin-6-yl-methyl)-imidazo[1,2-b]triazin-2-yl]bhenzamide, or a pharmaceutically acceptable salt thereof, and (ii) an EGFR tyrosine kinase inhibitor, or a pharmaceutically acceptable salt thereof wherein the cancer has an aberration in the c-MET pathway. 
     
     
         27 . The method of  claim 26 , wherein the cancer further has an aberration in the EGFR pathway. 
     
     
         28 . The method of  claim 26 , wherein the aberration in the c-MET pathway is c-MET gene amplification. 
     
     
         29 . The method of  claim 26 , wherein the cancer is progressed after EGFR inhibitor treatment. 
     
     
         30 . The method of  claim 26 , wherein the subject has developed resistance to EGFR inhibitor treatment.